Estudo das interações dos surfactantes iônicos SDS, CTAC e HPS e miltefosina com membranas de leishmania, macrófagos e eritrócitos

• Autor(a) principal: Cardoso, Éder Jéferson Souza
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UFG
• Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/13161
• topic: Surfactante; Miltesfosina; Eritrócito; Fluidez da membrana; Ressonância paramagnética eletrônica; Surfactant; Miltefosine; Erythrocyte; Membrane fluidity; Electron paramagnetic resonance; CIENCIAS BIOLOGICAS::BIOFISICA::BIOFISICA MOLECULAR

Miltefosine (MT) is an internationally approved oral drug for the treatment of leishmaniasis, however, its mechanism of action is not yet well established. Understanding the mechanism of action of compounds with leishmanicidal activity is important to help in the search for new drug prototypes with greater activity and fewer side effects. Surfactants are compounds widely used in the industry in the manufacture of soap, shampoos and other cosmetics. They are usually classified according to the molecular charge, and may be nonionic, anionic, cationic or zwitterionic (or amphoteric) when they have a positive and negative charge in the same compound. Electron Paramagnetic Resonance (RPE) spectroscopy associated with the spin-label method was used to compare the interactions of MT and the surfactants Sodium Dodecyl Sulfate (SDS, anionic), Cetyl Trimethyl Ammonium Chloride (CTAC, cationic) and N, N-dimethyl-3-ammonio-1-propanesulfonate (HPS, zwitterionic) with the membranes of Leishmania (L.) amazonensis, erythrocyte and macrophage. All compounds increased the molecular dynamics of membrane proteins; however, SDS caused the smallest increase in parasite and erythrocyte membrane dynamics and was also the least effective in antileishmanial activity, cytotoxicity in macrophages J774.A1 and hemolytic potential in both PBS and whole blood. It was detected, in blood plasma, the albumin stiffness caused by 2.5 mM SDS due to the electrostatic and hydrophobic interactions of the compound with the protein. CTAC did not show significant differences in relation to the other compounds, but at higher cell concentrations (>1x109 cells/mL), it showed high activity against the L. amazonensis promastigotes, besides being the most cytotoxic to macrophages J774.A1. For all the experiments, the zwitterionic molecules HPS and MT did not present significant differences between them. The data suggest the possibility of using cationic or zwitterionic surfactants in formulations containing leishmanicides, aiming at the treatment of cutaneous leishmaniasis.